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Biomedical subjects

M Yonezawa

Publications and source records attributed to M Yonezawa.

At least 37 records · Page 2Linked to original sources

[Role of national insurance pharmacies in community complete home care networks--home TPN and home care supported by local national insurance pharmacies].

The reforms in the medical system and introduction of home care insurance have brought great changes to national health insurance pharmacies. In April 1998, Dr. Hirai became new director of the Chiba Togane Hospital. The development of a community complete medical system was included in a restructuring of the hospital, and various reforms were begun. A system covering all aspects of the medical/pharmaceutical field was started in August 1998. For its part, the Sanbu-gun Pharmacists Association began accepting prescriptions outside the hospital, and regular meetings for the exchange of knowledge were held with members of the physicians and pharmacists associations. After building a relationship of trust in this way, a community complete home treatment system was begun in July 1999 with Togane Hospital functioning as its backup support hospital. To date, home TPN terminal care has been provided in cases of terminal cancer, incurable neurological diseases, and for the very aged and patients with cerebrovascular impairments. Any general pharmacy in the region can participate in the program to fill prescriptions for TPN, provided that the pharmacist him or herself so wishes, establishes a clean bench at the pharmacy, and undergoes training at Togane Hospital on the preparation of i.v. medicines in order to function responsibly in this capacity. These pharmacies are called satellite pharmacies, and at present there are four of them located with a good balance within the region. These satellite pharmacies prepare liquid medications for TPN, including narcotics, and oral medicines following the prescriptions written by the physician from the hospital who is serving as the primary home treatment physician. The pharmacy also delivers the medicines to the home of the patient. The pharmacist checks the status of remaining TPN liquids and oral medicines and informs the primary home physician and support hospital by e-mail or fax, so that everyone shares the same information. The success or failure of home TPN from a general pharmacy depends on the formation of a digital network in order to share information using the Internet and a back-up system for unconditional support by the support hospital in times of patient emergency. In our region, these conditions have been fulfilled.

Community Networks↗

A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells.

We have isolated a gene from stomach fibroblasts encoding novel proteins containing two follistatin modules which might bind TGF-beta-related growth factors and a single epidermal growth factor (EGF)-like domain which is closely related to EGF/Neuregulin (NRG) family growth factors. Sequence analysis revealed novel cDNA clones, the protein products of which were designated tomoregulin (TR) and consisted of at least three isoforms which were distinguished by their cytoplasmic domains. The cytoplasmic domains in all isoforms were short and contained potential G-protein activating motifs. Precursors of TR (Pro-TR) are glycosylated transmembrane proteins. Two secreted soluble forms resulting from proteolytic cleavage were distinguished by the presence or absence of the EGF-like domain. The EGF-like domain of TR was highly conserved compared to EGF/NRG family growth factors with the exception of an arginine to histidine substitution at position 39 (Arg --> His 39). Soluble TR stimulated erbB-4 tyrosine phosphorylation in MKN 28 gastric cancer cells, although it was weak compared to neuregulin-induced erbB-4 tyrosine phosphorylation; this suggests that TR might be a ligand for erbB-4- or erbB-4-related receptor tyrosine kinase. TR may have important roles in normal development of middle to late stages of embryos and maintenance of adult central nervous system tissues as high expression of TR mRNAs was observed in these tissues. The modular features suggest multiple roles for TR; these include functioning as a ligand for erbB- receptor, a regulator of TGF-beta-related growth factor signaling by direct interaction through the follistatin modules, and a G-protein-coupled receptor.

Amino Acid Sequence↗

Interleukin-8 potentiates the effect of interleukin-1-induced uterine contractions.

The aim of this research was to study the effect of exogenous interleukin (IL)-8, IL-1 and IL-8 + IL-1 on uterine contractions in rabbits. Four equal groups of non-pregnant rabbits (n = 24) were investigated using either placebo or experimental drugs in the form of vaginal suppositories. The suppositories contained human recombinant IL-8 (200 ng), IL-1 (200 ng), IL-8 (200 ng) + IL-1 (200 ng) or vehicle Witepsol base, 500 microliters). Subsequently, the plasma concentration of prostaglandin (PG) E2 was estimated 3 h after the last dose of treatment. Neutrophil infiltration in the endometrial tissue was studied with anti-rabbit RT2 staining. Suppositories with IL-1 and IL-8 + IL-1 produced contractile responses with increased frequency (P < 0.003, P < 0.0005) and amplitude (P < 0.0001) in vivo, compared with vehicle. IL-1 and IL-8 + IL-1 also caused similar contractile effects with increased frequency (P < 0.01, P < 0.0007) and amplitude (P < 0.0001) in an in-vitro experiment than vehicle. The frequency and amplitude of uterine contractions were more significant with IL-8 + IL-1 than that of IL-1, both in vivo (P < 0.002, P < 0.05) and in vitro (P < 0.005, P < 0.01). IL-8 did not induce any contractions. Prostaglandin concentration was increased approximately 8-fold with IL-8 + IL-1 (P < 0.0001) and 2.5-fold with IL-1 treatment (P < 0.0001). Neutrophil numbers were significantly increased with IL-8 + IL-1 > IL-8 > IL-1 (P < 0.002, P < 0.0003 and P < 0.008) compared with vehicle. Our data suggest that IL-8 stimulates IL-1-induced uterine contractions through PGE2 production and could be an important process during labour and delivery.

Animals↗

In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone.

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 microgram/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 microgram/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 microgram/ml) and M. pneumoniae (MIC90, 0.0313 microgram/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 microgram/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.

Administration, Oral↗

Vasospasms of cerebral arteries in hyperemesis gravidarum.

Hyperemesis gravidarum is associated with nausea and vomiting during the 1st trimester of pregnancy. We report 2 cases of hyperemesis gravidarum associated with vasospasms of cerebral arteries recognized by magnetic resonance imaging angiography. The hyperemetic condition of the patients improved after fluid and electrolyte replacement therapy.

Adult↗

Antibacterial activity of quinolones against coagulase-negative staphylococci and the quinolone resistance-determining region of the gyrA genes from six species.

Antibacterial activity of quinolones against three species of coagulase-negative staphylococci was investigated. Tosufloxacin and sparfloxacin exhibited potent activities against Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus saprophyticus compared with other quinolones tested. From the analysis of the DNA sequence in the quinolone resistance-determining region (QRDR), greater than 80% homology was recognized in coagulase-negative staphylococci. A series residue was conserved in all six species at the position corresponding to position 84 in Staphylococcus aureus.

Anti-Infective Agents↗

Molecular cloning of the nemA gene encoding N-ethylmaleimide reductase from Escherichia coli.

Using the gene mapping membrane technique, we identified a gene (nemA) that encodes N-ethylmaleimide reductase in Escherichia coli. The open reading frame encodes a polypeptide of 365 amino acids with a molecular mass of 39,514 Da. The deduced amino acid sequence showed a high degree of homology (87% identical) with the pentaerythritol tetranitrate reductase of Enterobacter cloacae and the morphinone reductase of Pseudomonas putida (52% identical).

Amino Acid Sequence↗

The effects of unsaturated fatty acids, oxidizing agents and Michael reaction acceptors on the induction of N-ethylmaleimide reductase in Escherichia coli: possible application for drug design of chemoprotectors.

Menadione and dimethyl maleate, Michael reaction acceptors, induced N-ethylmaleimide (NEM) reductase activity in Escherichia coli strain DH5a. Linoleic acid also induced NEM reductase activity, but oleic acid, which is less susceptible to lipid peroxidation than linoleic acid, did not induce NEM reductase activity. In addition, NEM reductase activity was induced by menadione and linoleic acid also in strain DH5, Y1088 and Y1090. Linoleic acid is not a Michael reaction acceptor, but is known to produce Michael reaction acceptors such as alkenals and 4-hydroxyalkenals as a result of free-radical-initiated lipid peroxidation. Thus, our findings suggested that lipid peroxidation was involved in the induction of NEM reductase by linoleic acid. The electrophilic property of Michael reaction acceptors provides the signal for induction of phase II enzymes such as glutathione S-transferase and quinone reductase in mammals. The inducer potency of phase II enzymes has been used to design chemoprotective drugs. Therefore, the inducible nature of this enzyme will serve not only for the elucidation of its physiological function, but also for the evaluation of chemoprotective drugs.

Enzyme Induction↗

Two types of X-ray-induced radioresistance in mice: presence of 4 dose ranges with distinct biological effects.

Preirradiation with 0.05 Gy of X rays 2 months before a second exposure to a mid-lethal dose significantly enhanced the survival rate in both female and male ICR strain mice. The radioresistance was observed between 2-2.5 months after exposure to 0.05 Gy. It did not appear within 1.5 months, and disappeared after 3 months. This radioresistance was induced only by whole-body preirradiation (not by partial irradiation of the head or the trunk). On the other hand, preirradiation with 0.30 Gy as well as 0.50 Gy resulted in radioresistance 2 weeks later, but not 2 months later. The radioresistance was induced by whole-body preirradiation or partial preirradiation of the trunk. No radioresistance was evident after exposure of intermediate preirradiation doses of 0.15 and 0.20 Gy administered before 2 months and 2-5 weeks, respectively. The present and previous results show that the biological effects of ionizing radiation may be distinguished with the following four radiation dose ranges; (1) below 0.025 Gy: no radioresistance after 2 months; (2) 0.05-0.10 Gy: significant radioresistance after 2-2.5 months; (3) 0.20 Gy: no radioresistance after 2-5 weeks; and (4) 0.30-0.50 Gy or more: significant radioresistance after 2 weeks. These results conflict with previous findings of the biological effects of ionizing radiation in which the radiation hazard increases in relation to increasing accumulated doses. Some stimulation, in addition to adaptation, by low dose irradiation may have occurred.

Adaptation, Physiological↗

Hyperthermia induces apoptosis in malignant fibrous histiocytoma cells in vitro.

The effect of mild hyperthermia on a cultured rat malignant fibrous histiocytoma (MFH) cell line, MFH-2NR, was investigated. MFH cells in log-phase (growing phase) were heated at 41 degrees-44 degrees C for 1 hr. Hyperthermic treatment at 41 degrees C did not substantially affect cell proliferation and treatment at 44 degrees C caused necrosis. After hypothermic treatment at 42 degrees or 43 degrees C, proliferation of MFH cells was arrested and morphological changes characteristic of apoptosis, cell shrinkage accompanying apoptotic bodies and chromatin condensation, became apparent. Hyperthermia-induced apoptosis was further confirmed by terminal deoxynucleotidyl transferase staining and a ladder pattern on agarose gel electrophoresis. Flow cytometric analysis indicated that the population in the G1 phase of the cell cycle significantly decreased with a concomitant increase in apoptotic cells, indicating that apoptosis might occur mainly in the G1 phase population.

Animals↗

Cystine deprivation induces oligodendroglial death: rescue by free radical scavengers and by a diffusible glial factor.

In this study we examined the effect on oligodendroglial survival of exogenous cystine deprivation. Oligodendroglia isolated from mixed glial primary cultures derived from brains of 1-day-old rats, and then grown for 3 days, were markedly dependent on extracellular cystine for survival. The EC50 values for cystine for a 24-h exposure ranged from 2 to 65 microM. After 6 h of cystine deprivation, the cellular glutathione level decreased to 21 +/- 13% of the control. Free radical scavengers (alpha-tocopherol, ascorbate, idebenone, and N-tert-butyl-alpha-phenylnitrone) were protective against cystine deprivation but had no effect on the glutathione level. An iron chelator, desferrioxamine mesylate, also was protective. These findings suggest that intracellular hydroxyl radicals are important for this toxicity. In contrast to the observations in 3-day-old cultures, the dependence on exogenous cystine for cell viability was not observed consistently in oligodendroglia cultured for 6 days before the onset of cystine deprivation. Several observations suggested that this loss of cystine dependence was due to a diffusible factor. Sensitivity to the toxicity of cystine deprivation in day 6 cultures increased as the volume of medium was increased from 0.3 to 2 ml. Furthermore, preincubation of cystine-depleted medium with astrocyte cultures eliminated the toxicity of the cystine deprivation. HPLC assay of the conditioned cystine-depleted medium showed no significant change in cystine or cysteine concentration. We conclude that oligodendroglia are highly susceptible to cystine deprivation in day 3 cultures and that this susceptibility is due to the accumulation of intracellular free radicals in the setting of glutathione depletion. The resistance of day 6 oligodendroglial cultures is caused at least in part by a diffusible factor.

Animals↗

Mutations in the gyrA and grlA genes of quinolone-resistant clinical isolates of methicillin-resistant Staphylococcus aureus.

The mutations in the quinolone-resistance determining regions (QRDR) of the gyrA, gyrB and grlA genes and in the norA gene from five clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) were examined by DNA sequencing. The mutation from Ser84 to Leu in GyrA was associated with relatively high-level resistance to quinolones, whereas the mutation from Glu88 to Gly or Lys in GyrA was associated with low-level resistance to quinolones. Mutations of the grlA gene were observed at codon 80 (Ser80) or 84 (Glu84), independent of the mutations of gyrA. No mutations were observed in either the gyrB or norA genes.

Anti-Infective Agents↗

Comparison of plasma concentrations of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) in normal and preeclamptic pregnancies.

The study was undertaken to measure both plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) concentrations in normal and preeclamptic pregnancies to elucidate the mechanisms of plasma volume regulation during pregnancy. The mean plasma AVP concentration in healthy pregnant women was much lower than nonpregnant controls; however, the concentration in preeclamptic patients was similar to that in the comparative period of normal pregnancy. Despite volume expansion, the mean plasma concentration of ANP in normal pregnancy showed no changes compared to nonpregnant controls. The concentration of plasma ANP in patients complicated by mild preeclampsia was higher than that in normal pregnant women. The concentration of plasma ANP in those with severe preeclampsia was much higher roughly in proportion to the severity of the disease. It is inferable that the lowered concentration of plasma AVP is involved in plasma volume expansion in normal pregnancy, largely but not in a depletion of plasma volume in preeclampsia. The elevated concentration of plasma ANP appears to be closely related to impaired plasma volume expansion in preeclampsia.

Adult↗

Microwave digestion using dual PTFE containers for analysis of trace elements in small amounts of biological samples.

The analysis of trace elements in biological samples is essential to extend our knowledge on human health and disease. Inductively coupled plasma mass spectrometry (ICP-MS) makes it possible to simultaneously determine these elements in trace amounts. Before analysis, however, biological samples such as organs and tissues must be liquefied and extra organic materials must be decomposed by acid digestion. We established a method of microwave digestion using dual PTFE containers to minimize the amount of samples. Samples (35-45 mg) of standard reference materials, bovine liver (1577a, NIST) and fish flesh (MA-A-2, IAEA), were weighed in PTFE-PFA vials and a small amount of nitric acid (0.5 ml) was added. The vials were sealed and two PTFE-PFA vials were placed in a PTFE-TFM vessel containing 6 ml of pure water. Then the vessels were placed in a rotor and the samples were digested for 38 min in a microwave oven according to a pre-set program. After the program was completed, the samples were analyzed by ICP-MS. The determined values of elements of the microwave-digested samples matched the certified values of the standard reference materials. Therefore, the digestion using dual containers was successfully applied to small samples.

Animals↗

Comparative study of erythrocyte deformability in maternal and cord blood.

To elucidate the rheological difference in maternal and fetal blood by determining erythrocyte deformability, 20 pairs of mothers and newborns, and 20 nonpregnant women were studied. Erythrocyte deformability was measured by means of an electron spin resonance method. Erythrocyte deformability was dependent on the hematocrit, and there was an optimal hematocrit value at which the deformation was maximal. The hematocrit at which the deformability was maximal showed a lower value (32 to 35%) in maternal blood; conversely, a higher value (47 to 50%) occurred in fetal blood than that (40 to 43%) in nonpregnant control women. When the hematocrit of the red blood cell suspension in dextran solution was adjusted to 40% (nonpregnant blood), 35% (maternal blood), and 50% (fetal blood), the deformability of fetal erythrocytes was significantly higher than maternal blood (P < 0.05), and its value was almost similar to that of nonpregnant control women. Based on our results, erythrocyte deformability of fetal blood is much higher compared with the maternal blood, suggesting the effective oxygen supply to the fetal tissues even in the circumstances of lower oxygen tension.

Adult↗